The major objective of this project is to investigate patients with glomerulonephritis and with systemic disorders associated with glomerulonephritis, with particular reference to natural history and immunopathogenesis. It is proposed that the induction of human glomerulonephritis is due to multiple rather than to single causal factors; the investigations attempt to define some of these multiple potential modulating factors. The precise nature of the renal disease will be defined in renal biopsies by light microscopy, by electron microscopy, and by immunofluorescence microscopy. Particular attention will be paid to the role of circulating immune complexes, including their level, size, and ability to activate platelets. Factors that will be studied serially will be the complement system, aspects of hemostasis and reticuloendothelial system function. These factors will be analyzed in relation to the precise type of renal histologic change observed. Serial sequential observations will be made after treatment with various therapeutic agents having different actions, but which have in common the capacity to produce measurable effects rapidly. The effect of each agent on the course of the disease, on the modulating factors measured, and on the renal histologic changes will be assessed. Studies will be done in patients with lupus nephritis, with various forms of diffuse proliferative, with focal proliferative, and with membranous glomerulonephritis.